Suppression of IL-23-mediated psoriasis-like inflammation by regulatory B cells

Abstract

Psoriasis is an inflammatory cutaneous disease mediated by T-cell dependent immune responses; however, B cells are also considered to play an important role its development. Regulatory B cells (Bregs) regulate immune responses negatively through interleukin-10 (IL-10) production. This study aimed to investigate the role of Bregs in IL-23-mediated psoriasis-like inflammation in mice. Psoriasis-like inflammation was induced in B cell-specific phosphatase and tensin homolog (PTEN)-deficient mice, in which Bregs were significantly expanded, and in their controls, by intradermal injection of 20 μL phosphate-buffered saline (PBS) containing 0.5 μg rmIL-23 into one ear, every other day for 16 days. IL-23-mediated psoriasis-like inflammation was suppressed in B cell-specific PTEN-deficient mice along with decreased ear thickness and epidermal thickness on day 15. Moreover, adoptive transfer of B1 B cells suppressed IL-23-mediated psoriasis-like inflammation. rmIL-23-injected B cell-specific PTEN-deficient mice showed expanded regulatory T cells (Tregs) in the spleen and draining lymph nodes along with increased Bregs. Further, T helper (Th) 17 differentiation in the rmIL-23-injected ear was suppressed in B cell-specific PTEN-deficient mice. Overall, these results indicate that increased Bregs suppress IL-23-mediated psoriasis-like inflammation through Treg expansion and inhibition of Th17 differentiation. Thus, targeting Bregs may be a feasible treatment strategy for psoriasis.

Spatial transcriptomics stratifies psoriatic disease severity by emergent cellular ecosystems

“…Varying ratios of B cells have been found in both the peripheral blood and lesional skin of patients with PsO and correlate with the presence of arthritis and cutaneous disease severity (47)(48)(49). More recently, depletion of IL-10-producing regulatory B cells (B regs ) has also been proposed as a trigger for activation of the IL-23/T H 17 axis (50,51). An enrichment of B reg progenitors and concomitant loss of mature IL-10-producing B regs was observed in patients with PsO compared with healthy individuals, and this imbalance was reversed by biologic therapy (52).…”

Skin Barrier Dysregulation in Psoriasis

“…They have a reduced prevalence in the circulation of psoriasis patients, and their progenitor cell has an increased prevalence, suggesting psoriatic states could prevent their differentiation [ 156 ]. In two mouse models, Breg presence is associated with a reduction in skin lesion severity, less production of IFN-γ and IL-17, decreased Th17 differentiation, and increased Treg differentiation [ 157 , 158 ]. These findings suggest psoriasis pathogenesis may involve Breg cell dysregulation, and that future therapies may involve their reconstitution.…”

Shared Genetic Risk Factors for Multiple Sclerosis/Psoriasis Suggest Involvement of Interleukin‐17 and Janus Kinase–Signal Transducers and Activators of Transcription Signaling

“…81 Nevertheless, regulatory B-cell involvement in responses to the phosphodiesterase 4 inhibitor, apremilast, has recently been reported, 82 and they are able to suppress IL-23-mediated inflammation. 83 Previous research showed tonsils from psoriasis patients had a lower germinal center to marginal zone area ratio, 84 and germinal center affinity maturation plays an important role in MS. 85 B-cell activation is believed to be enhanced by neutrophil extracellular traps in MS, 86 as well as in lupus. 87 Although neutrophil extracellular traps have been found to promote psoriatic inflammation, particularly through Th17, 29,88 it has yet to be investigated whether they assist B-cell maturation in a similar way to other diseases.…”

“…Although the role of B cells has been elucidated in MS, 1 they have been less well studied in psoriasis, potentially because they are detected in smaller numbers than T cells in lesional skin 81 . Nevertheless, regulatory B‐cell involvement in responses to the phosphodiesterase 4 inhibitor, apremilast, has recently been reported, 82 and they are able to suppress IL‐23‐mediated inflammation 83 . Previous research showed tonsils from psoriasis patients had a lower germinal center to marginal zone area ratio, 84 and germinal center affinity maturation plays an important role in MS 85 .…”